Double-strand breaks (DSBs) occur spontaneously within chromosomal DNA and can be induced by exposure of cells to various mutagens. Physical agents (e.g. Xrays) and chemical clastogens (e.g. the anti-tumor drugs bleomycin and phleomycin) generate DSBs in DNA. Induction of DSBs results in higher levels of mutagenesis, aneuploidy, and gross chromosomal aberrations. Inefficient repair of such breaks is likely to play a role in the etiology of carcinogenesis and aging. Many of the proteins involved in DSB repair are conserved in yeast and mammalian cells including several members of the RAD52 epistasis group. The repair of different types of DSBs in wildtype and rad- yeast strains has been examined in great detail during the past year. Plasmid-mediated in vivo expression of the HO endonuclease (producing a single cohesive-ended DSB) and EcoRI (yielding multiple cohesive-ended DSBs) transiently arrested Rad+ cells and permanently arrested rad52 cells in G2. Remarkably, the arrested rad52 cells remained viable throughout each induction. Growth could be rescued in media which turned off expression of HO and EcoRI, indicating that the cohesive-ended DSB's could be repaired. Growth arrest was observed in RAD52 group mutants, but not in rad1, rad3, or rad9 strains. rad9 checkpoint mutants did not arrest in G2 and died rapidly when HO and EcoRI were expressed. Expression of PvuII (multiple blunt-ended DSBs) induced transient G2-arrest in Rad+ strains and permanent arrest of rad52 cells; however, viability was reduced in both strains. Expression of endonucleases also induced high levels of recombination and aneuploidy. The available evidence suggests that the repair of X-ray-induced DSB's is very different from the repair of endonuclease-induced DSBs.